Background: Myonectin (CTRP15) is a newly discovered myokine with important metabolic functions. It was shown that circulating myonectin levels decreased in obesity. Objectives: The present study investigated the effect of 8 weeks of progressive resistance training (PRT) on serum myonectin levels in rats following a high-fat diet plus sucrose solution. Methods: A total of 32 male Wistar rats were randomly divided into high-fat diet plus sucrose (HFDS) and standard diet (SD) groups. After 12 weeks, each group was divided into sedentary and training groups. The animals in training groups were subjected to a PRT program (3 days/week, for 8 weeks). Flexor hallucis longus (FHL) and gastrocnemius muscle weights, epididymal and retroperitoneal fat weights, serum glucose, insulin, myonectin, and homeostasis model assessment of insulin resistance (HOMA-IR) were measured in this study. Results: The results of the study revealed that HFDS increased weight gain, fat weight, serum glucose, and HOMA-IR levels and decreased muscle weights and serum myonectin levels. Eight weeks of PRT increased serum myonectin levels and FHL and gastrocnemius muscle weights and decreased retroperitoneal fat weight. Conclusions: The results suggest that PRT may be an efficient intervention to enhance serum myonectin levels, which is associated with the improvement of body composition.