Objective: Huannao Yicong Decoction(还脑益聪方, HYD), an effective herbal formula against Alzheimer’s disease(AD), has been proven to have neuroprotective action in amyloid β-protein_(1-42))(Aβ_(1-42))-induced rat model. This study was designed to characterize mechanisms by which HYD leads to suppression of inflammation and apoptosis in the brains of Aβ_(1-42)-induced rat. Methods: A total of 72 rats were divided into 6 groups, which were referred to as: sham operation group, model group, donepezil-treated group, HYD low-dose group(HYDL), HYD middle-dose group(HYDM) and HYD high-dose group(HYDH). Rats in HYDL, HYDM and HYDH were injected with Aβ_(1-42) at the CA1 region of hippocampus to form AD model and were fed the HYD extract at different dose of 3.78, 7.56 and 18.90 g crude drug/kg. The behavioral changes of rats were evaluated by Morris water maze(MWM) before sacrifice. Pathological changes of the brain tissue were evaluated using hematoxylin eosin(HE) staining. The levels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α) were measured by radioimmunoassay. The levels of Aβ and proteins that are associated with apoptosis such as B-cell lymphoma-2 protein(Bcl-2), Bcl-2-associated X protein(Bax), cysteine-aspartic protease(caspase)-3,-8,-9 and-12 in serum were measured by immunohistochemistry. Results: Compared with the sham operation group, the spatial learning and memory abilities of AD rats were significantly decreased(P<0.05 or P<0.01; Expressions of IL-1, TNF-α, Aβ and apoptosis-signaling proteins caspase-3,-8,-9,-12 were significantly up-regulated(P<0.05 or P<0.01). The ratio of Bcl-2 to Bax were significantly decreased in the model group(P<0.01). When treated with HYD extract, the spatial learning and memory abilities of AD-model rats were significantly increased(P<0.05 or P<0.01), IL-1, TNF-α, Aβ, caspase-3,-8,-9 and-12 were down-regulated(P<0.05 or P<0.01), and the ratio of Bcl-2 to Bax were reduced(P<0.05 or P<0.01). Conclusions: HYD extract can improve the learning and memory ability deficits, alleviate the inflammatory response and pathological manifestations induced by Aβ_(1-42) injection in the rat model of AD. HYD down-regulates the levels of IL-1, TNF-α and Aβ, and decreases the rate of apoptosis by modulating apoptosis-signaling-related proteins such as caspase-3,-8,-9, and-12. Objective: Huannao Yicong Decoction, an effective herbal formula against Alzheimer’s disease (AD), has been proven to have neuroprotective action in amyloid β-protein (1-42)) (Aβ 1-42 )) - induced rat model. This study was designed to characterize mechanisms by which HYD leads to suppression of inflammation and apoptosis in the brains of Aβ 1- (1-42) -induced rat. Methods: A total of 72 rats were divided into 6 groups , which were referred to as: sham operation group, model group, donepezil-treated group, HYD low-dose group (HYDL), HYD middle- dose group (HYDM) and HYD high-dose group HYD and HYDH were injected with Aβ_ (1-42) at the CA1 region of hippocampus to form AD model and were fed the HYD extract at different doses of 3.78, 7.56 and 18.90 g crude drug / kg. The behavioral changes of rats were evaluated by Morris water maze (MWM) before sacrifice. Pathological changes of the brain tissue were evaluated using hematoxylin eosin (HE) staining. The leve ls of interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-a) were measured by radioimmunoassay. The levels of Aβ and proteins that are associated with apoptosis such as B-cell lymphoma-2 protein ), Bcl-2-associated X protein (Bax), cysteine-aspartic protease (caspase) -3, -8, -9 and -12 in serum were measured by immunohistochemistry. and memory abilities of AD rats were significantly decreased (P <0.05 or P <0.01; Expressions of IL-1, TNF-α, Aβ and apoptosis- signaling proteins caspase-3, -8, -9, The ratio of Bcl-2 to Bax were significantly decreased in the model group (P <0.01). When treated with HYD extract, the spatial learning and memory abilities of AD-model rats were The levels of IL-1, TNF-α, Aβ, caspase-3, -8, -9 and -12 were down-regulated (P <0.05 or P <0.01) ratio of Bcl-2 to Bax were reduced (P <0.05 or P <0.01). Conclusions: HYD extract can impralleviate the inflammatory response and pathological manifestations induced by Aβ_ (1-42) injection in the rat model of AD. HYD down-regulates the levels of IL-1, TNF-α and Aβ, and decreases the rate of apoptosis by modulating apoptosis-signaling-related proteins such as caspase-3, -8, -9, and-12.