In an attempt to know the role of nitric oxide in the disease of insulin-dependent diabetic mellitus (IDDM), the present study examined the change of nitric oxide synthase (NOS) both the activity and gene expression in cerebrocortex of streptozotocin-induced diabetic rats (STZ-diabetic rats). The activity of NOS determined by conversion of [3H] L-arginine to [3H] L-citrulline was markedly decreased in STZ-diabetic rats. Northern blot showed that STZ-diabetic rats expressed a lower mRNA level of neuronal NOS (nNOS). Western blot showed a similar decrease of nNOS in STZ-diabetic rats. However, the NOS activity was increased in rats receiving repeated supply of glucose named glucose-challenged rats. Although the mRNA level of nNOS was not changed in the glucose-challenged rats, the immunoblot of nNOS was also decreased in glucose-challenged rats. These findings suggested that NOS was lowered in the brain of STZ-diabetic rats in a way unrelated to the increase of glucose.