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• Leptin increases the expression of its own receptor and signaling transducer, JAK2. • Leptin reduces Gs to Gi protein ratio in receptor- and JAK-2-dependent manner. • It also decreases the expression of BK Caα and BK Caβ channel subunits. • These findings collectively suggest that leptin would exert an inhibitory influence on against-induced uterine relaxation in late pregnancy. Obesity can have a significant impact on pregnancy outcomes by compromising the ability of the uterus to relax, which increases the likelihood of conditions such as preterm labor. One of the key pathways responsible for uterine relaxation is the β-adrenergic signaling pathway, and it is well-documented that obesity, often linked to a high-fat diet, can disrupt this pathway within the uterine environment. Hyperleptinemia is a significant feature of pregnancy as well as obesity. However, the effect of leptin on β-adrenergic signaling pathway has not been studied. In the present study, we studied the effects of leptin on transcriptions of the major proteins defining the β-adrenergic signaling pathway in pregnant rat uterus. Leptin treatment at a supraphysiological concentration to pregnant rat uterine strips increased the mRNA and protein expressions of Gs protein but not the mRNA of β 2 - and β 3 -adrenoceptors. It also enhanced the expression of Gi-protein, but not the Gq protein. Nevertheless, the mRNA ratio of Gs to Gi protein experienced a significant decrease. Further, leptin reduced the transcription of BK Caα and BK Caβ channel subunits. In leptin-stimulated tissues, there was also an increase in the expression of leptin receptor and JAK-2. In conclusion, leptin decreases the ratio of Gs to Gi proteins and BK Caα and BK Caβ channel subunits suggesting hyperleptinemia is a likely factor inducing uterine relaxant dysfunction in obesity. [ABSTRACT FROM AUTHOR]