The effects of N^G-Nitro-_L-arginine-methyl ester (_L-NAME), an inhibitor of nitric oxide (NO) synthase, on decidual cell proliferation were examined to investigate possible NO depletion-mediated mechanisms of reproductive toxicity. Mid-to-late pregnant rats were injected intraperitoneally with _L-NAME (100 mg/kg body weight) and 5-bromo-2′-deoxyuridine (BrdU, 100 mg/kg body weight) at 12 hr and 1 hr before sacrifice, respectively, on day 13.5, 17.5, or 21.5, and the BrdU-positive proliferating decidual cells were detected. In control rats, proliferating decidual cells were observed sporadically on days 13.5 and 17.5; however, fewer such cells were observed at day 21.5. _L-NAME reduced the number of proliferating decidual cells by approximately half at days 13.5 and 17.5 but not at day 21.5. These results suggested that in mid-to-late pregnant rats, decidual cell proliferation was maintained by a mechanism involving NO signaling, and NO depletion reduced it only to a limited extent. The absent effect at day 21.5 may be due to the low incidence of proliferating decidual cells or the changing role of NO near the term of pregnancy.