Abstract: Objective To observe the effect of leptin on PI-3K activity in C2C12 myotubes and C2C12 myotubes transferred with OBRb gene, and to find out a possible signaling pathway of leptin acting directly on peripheral tissues. Methods PI-3K activity was measured in immunopre-cipitate with antibody against janus kinase 2CJAK2). The32P radioactivity incorporated into PI-3P was quantified by a phosphoimager. Results In C2C12 myotubes, the treatment with 10 ng/ml of leptin for 10.30,60 min, did not significantly affect JAK2-mediated PI-3K activity when compared with untreated control cells. In C2C12 myotubes transferred with OBRb gene, the treatment with the same dose of leptin for 60 min caused a 107% increase in PI-3K activity when compared with untreated control cells and a 90% increase when compared with the control group. In C2C12 myotubes, after the treatment with 50 ng/ml of leptin for 10 min, the PI-3K activity was 68% higher than that in untreated control cells. As the dose of leptin rose to 100 ng/ml, the PI-3K activity decreased slightly and was 49% higher than that in the control cells. Conclusion Leptin activates JAK2-me-diated PI-3K. This effect can be improved by transferring OBRb gene to increase the OBRb receptor expression.