A major challenge in diabetic disease is the systemic glucose handling mechanisms with little effort directed at it in the recent past. Spondias mombin is a flowering plant of the anacardiacae family that has been credited with anti-diabetic properties. This study evaluated the anti-diabetic activity of S. mombin, its effects on glucose transporter 4 (Glut-4) and adiponectin receptors signalling in streptozotocin-induced diabetic rats. Adult male Wistar rats (120-160g) were randomly divided into 4 groups. Group 1 were normo-glycemic control rats given regular rat chow and water. Group 2 served as negative hyperglycaemic control. Group 3 (High dose) and Group 4 (low dose) served as treatment groups which were pre-treated with 750mg/kg and 50mg/kg of S. mombin respectively for 21 days. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were done. Glut-4 and adiponectin expression were measured from the supernatant of the gastrocnemius homogenate using ELISA assay. Results were analysed using ANOVA with p<0.05. Results showed that at low doses, S. mombin modulated the glucose handling capabilities of diabetic rats via an insulin-like acting mechanism. S. mombin also significantly elevated adiponectin expression which has a direct correlation with insulin sensitivity. These effects were not magnified in the high dose group. S. mombin failed to potentiate Glut-4 expression in all tested groups. This study showed that the anti-diabetic activity of S. mombin acts via insulin-like mechanism. This is buttressed by the significant increase in adiponectin expression which is a direct correlate of insulin sensitivity.