Abstract: This experiment was conducted to study mechanisms of FSH regulating Sertoli cell proliferation. Sertoli cells of 2-3 week-old piglet were used as cell models, and cell viability, ELSIA and Western blot were used to explain the effect of FSH. The results were as follows: (1) From 0 to 50 ng·mL^-1, with the increase of the concentration of FSH, Sertoli cell number showed an upward trend(P<0.05); at 50 ng·mL^-1, effect of FSH on Sertoli cell proliferation was most significant; the concentration of intracellular cAMP also increased, following the increase of the concentration of FSH(P<0.05); (2) FSH begun to activate ERK1/2 cascade reaction 5 min after its affecting and the activating model had a periodicity; ERK1/2 inhibitor (PD98059 and U0126) could significantly inhibit the FSH-induced Sertoli cell proliferation and the expression of PCNA (proliferating cell nuclear antigen) (P<0.05); (3) Both of FSH and Forskolin could enhance cell proliferation and ERK1/2 activation (P<0.05), while Rp-cAMP and L-Ca²⁺ channel inhibitor (Verapamil) significantly both inhibited the FSHinduced cell proliferation and ERK1/2 activation(P<0.05); Rp-cAMP and Verapamil showed synergism effect (P<0.05). These results indicated that FSH could activate ERK1/2 via cAMP and Ca²⁺,which increased the expression of PCNA, and promoted Sertoli cell proliferation.