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Objective: To establish an efficacious and efficient fermentation method of enhancing the anti-adipogenesis effect of mulberry (Morus alba) leaves using Cordyceps militais.Methods: Dried mulberry leaves, dried mulberry leaves with 50% raw silkworm pupa and raw silkworm pupa were fermented with Cordyceps militais for 4 weeks at 25 ℃, after which the dried mulberry leaves and fermented product were extracted with 70% ethanol and subjected to high performance liquid chromatography (HPLC). The contents of cordycepin, pelargonidin, chlorogenic acid, iso-quercetin and caffeic acid were determined. We then used the 3T3-L1 cells to investigate whether extracts of fermentation enhanced anti-adipogenesis activity in vitro. Results: HPLC showed that fermentation changed the contents of cordycepin, pelargonidin, chlorogenic acid, iso-quercetin and caffeic acid. Furthermore, fermented dried mulberry leaves with 50% raw silkworm pupa had a better efficacy of anti-adipogenesis than dried mulberry leaves, fermented dried mulberry leaves and fermented silkworm pupa and inhibited triglycerides accumulation and glucose consumption. Additionally, fermented dried mulberry leaves with 50% raw silkworm pupa inhibited PPAR-γ signaling.Conclusions: Fermentation with Cordyceps militaris enhanced anti-adipogenesis efficacy of mulberry leaves.