AIM: To detect the resistin expression of white adipose tissue in diet-induced obese (DIO) versus diet-resistant (DR) rats, and to investigate the relationship of mutated resistin and 3T3-L1 preadipocytes differentiation. METHODS:RT-PCR and Weste Blot were used to detect gene/protein expression. 3T3-L1 cells were cultured, transfected,and induced to differentiation using 0.5 mmol/L 3-isobutyl-1-methyxanthine (MIX), 1 mg/L insulin, and 1μmol/Ldexamethasone. Oil red O staining was applied to detect the degree of preadipocytes differentiation. RESULTS:Expression of resistin mRNA was upregulated in DIO rats and downregulated in DR rats. However, the expression levels varied greatly within the groups. Sequencing of the resistin genes from DIO and DR rats revealed a Leu9Val (C25G) missense mutation within the signal peptide in one DR rat. The mutant resistin inhibited preadipocyte differentiation. Local experiments and Weste blotting with tagged resistin fusion proteins identified both mutant and wild type proteins in the cytoplasm and secreted into the culture medium. Computer predictions using the Proscan and Subloc programs revealed four putative phosphorylation sites and a possible leucine zipper motif within the rat resistin protein. CONCLUSION: Resistin-increased differentiation may be inhibited by the mutationcontaining precursor protein, or by the mutant non-secretory resistin isoform.