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The brain‐derived neurotrophic factor (BDNF) was first recognized for its roles in the peripheral and central nervous systems, and its complex functions on mammalian organs have been extended constantly. However, to date, little is known about its effects on the male reproductive system, including the steroidogenesis of mammals. The purpose of this study was to elucidate the effects of BDNF on testosterone generation of Leydig cells and the underlying mechanisms. We found that BDNF‐induced proliferation of TM3 Leydig cells via upregulation of proliferating cell nuclear antigen (
Pcna) and promoted testosterone generation as a result of upregulation of
steroidogenic acute regulatory protein (
Star),
3b‐hydroxysteroid dehydrogenase (
Hsd3b1), and
cytochrome P450 side‐chain cleavage enzyme (
Cyp11a1) both in primary Leydig cells and TM3 Leydig cells, which were all attenuated in Bdnf knockdown TM3 Leydig cells. Furthermore, the possible mechanism of testosterone synthesis was explored in TM3 Leydig cells. The results showed that BDNF enhanced extracellular signal‐regulated protein kinases 1 and 2 (ERK1/2) phosphorylation, and the effect was disrupted by
Bdnf deletion. Moreover, PD98059, a potent selective inhibitor of ERK1/2 activation, compromised BDNF‐induced testosterone generation and upregulation of
Star,
Hsd3b1, and
Cyp11a1. The
Bdnf knockdown assay, on the other hand, indicated the autocrine effect of BDNF on steroidogenesis in TM3 Leydig cells. On the basis of these results, we concluded that BDNF, acting as an autocrine factor, induced testosterone generation as a result of the upregulation of
Star,
Hsd3b1, and
Cyp11a1 via stimulation of the ERK1/2 pathway.
Our work proved that brain‐derived neurotrophic factor (BDNF) can promote proliferation and steroidogenesis of mouse Leydig cells via an autocrine pattern. We still speculated that BDNF can exert its diverse actions by other ways, such as endocrine or paracrine patterns. We also found that extracellular signal‐regulated protein kinases 1 and signaling was activated in this process, which could not be the only one pathway active in this process.