Objective To evaluate the effect of sevoflurane on the proliferation of neural stem cells (NSCs) in the ventricular/ subventricular zone of neonatal rats. Methods Forty?eight 7?day?old Sprague?Dawley rats, weighing 15 -20 g, were divided into three groups (n =16 each) using a random number table: control group (Con), 1% sevoflurane group (S1), and 3% sevoflurane group (S2). Rats in the control group inhaled air for 4 h. Rats in S1 and S2 groups inhaled 1% and 3% sevoflurane, respectively, for 4 h. Cell proliferation was detected by Nestin and 5?bromodeoxyuridine staining. Protein expression of Nestin, Cyclin D1, BMP2, and Smad4 in ventricular/ subventricular tissues was analyzed by Western blotting. Results Compared with the control group, the proliferation rate of NSCs was decreased significantly. Expression levels of Nestin and Cyclin D1 were downregulated, but expression levels of BMP2 and Smad4 were significantly upregulated after sevoflurane treatment ( P < 0.05). Conclusions Sevoflurane inhibits proliferation of NSCs in the ventricular/ subventricular zone of neonatal rats and the mechanism may be related to regulation of Cyclin D1, BMP2, and Smad4 expression.