Pro‐inflammatory and stress‐activated signalling pathways are important role players in the pathogenesis of obesity and insulin resistance. Obesity and type II diabetes are associated with chronic, low‐grade inflammation and elevated tumour necrosis factor‐α (TNF‐α) levels. There is increasing evidence that TNF‐α may play a critical role in skeletal muscle atrophy. However, the effects of obesity‐induced insulin resistance on these signalling pathways are poorly understood in skeletal muscle. Therefore, the present study addressed the effects of obesity‐induced insulin resistance on the activity of the ubiquitin ligases, nuclear factor‐κB, p38 MAPK and phosphoinositide 3‐kinase signalling pathways in the gastrocnemius muscle and compared these with muscle of standard chow‐fed control rats. Male Wistar rats were randomly allocated to a control diet group (standard commercial chow; 60% carbohydrates, 30% protein and 10% fat) or a cafeteria diet group (65% carbohydrates, 19% protein and 16% fat) for 16 weeks. Blood analysis was conducted to determine the impact of the model of obesity on circulating insulin, glucose, free fatty acids, TNF‐α and angiotensin II concentrations. The experimental animals were 18% heavier and had 68% greater visceral fat mass than their control counterparts and were dyslipidaemic. Significant increases in the ubiquitin ligase and MuRF‐1, as well as in caspase‐3 and poly‐ADP‐ribose polymerase cleavage were observed in the muscle of obese animals compared with the control rats. We propose that dyslipidaemia may be a mechanism for the activation of inflammatory/stress‐activated signalling pathways in obesity and type II diabetes, which will lead to apoptosis and atrophy in skeletal muscle.