Abstract: Objective To study the inhibitory effect of leptin on rotenone-induced apoptosis of human neuroblastoma SH-SY5Y cells. Methods A SH-SY5Y cell injury model was induced by rotenone and intervened with leptin. Viability of SH-SY5Y cells was assayed by MTT, apoptosis of SH-SY5Y cells was detected with trypan blue staining, morphology of SH-SY5Y cells was observed under inverted microscope, expression levels of Bcl-2, Bax, p-GSK-3β(Ser9), GSK-3β and α-synuclein were measured by Western blot and immunofuorescence, respectively. Results The rotenone-induced SH-SY5Y cell injury model was successfully established. The survival rate of SH-SY5Y cells was about 14% higher(P＜ 0.05), the apoptosis rate of SH-SY5Y cells was about 17% lower(P＜ 0.05), the α-synuclein expression level was signifcantly lower whereas Bcl-2 and p-GSK-3β expression was signifcantly higher after leptin intervention than before leptin intervention. Conclusion Leptin can signifcantly inhibit rotenoneinduced SH-SY5Y cell injury by up-regulating the Bcl-2/Bax ratio and down-regulating the expression of α-synuclein through the activity of GSK-3β.