Disturbances in hormonal signaling systems, in the adenylyl cyclase system (ACS) in particular, occur at early stages of diabetes mellitus (DM) and are one of the key causes of its complications. Since there is a correlation between the severity of DM and of disturbances in the ACS, the study of the ACS activity can be used to monitor DM and its complications and to evaluate effectiveness of their treatment. Comparatively recently, for treatment of the type 2 DM, there began to be used the intranasal insulin (I-I) and drugs increasing brain serotonin level, which effectively restore CNS functions. However, mechanisms of their action on peripheral tissues and organs with DM remain to be not understood. The goal of this work was to study effects. of I-I and intranasal serotonin (I-S) on the ACS functional activity in myocardium, ovary, and uterus of rats with a neonatal model of the type 2 DM. In tissues of diabetic rats there were revealed changes in regulation of adenylyl cyclase (AC) by guanine nucleotides and hormones that both stimulated and inhibited this enzyme, such changes being characterized by the receptor and tissue specificity. In diabetic rats, I-I restored the AC stimulating effects of isoproterenol in the myocardium, guanine nucleotides and gonadotropin in ovaries and relaxin in uterus, as well as the AC inhibitory effects of somatostatin in all tissues, and of noradrenaline in myocardium. Treatment with IS led to a partial restoration of the AC-inhibitory effect of noradrenalin in the diabetic myocardium, but did not affect regulation of AC by other hormones. These data indicate that I-I normalizes the ACS functional activity in myocardium and in tissues of the reproductive system of female rats with neonatal DM, whereas the effect of I-S on in the studied tissues is less pronounced. These results are necessary to be taken into account at development and optimization of strategy of use of I-I and I-S for treatment of DM and of its complications.