Intramyocellular diglycerides have been implicated in the development of insulin resistance. We aimed to evaluate the effect of weight loss, a well-known means for the improvement of insulin resistance, on intramyocellular diglycerides and triglycerides in type II diabetes. Participants were five obese women with type II diabetes (body mass index 37.5+/-1.9 kg/m(2)), who participated in a weight loss program. The aim of the program was a reduction in body weight by 10%. Muscle biopsies were obtained before and after weight loss. The intervention induced a marked reduction in intramyocellular triglycerides by 77.7+/-13.1%, whereas no significant differences were observed for diglycerides before and after weight loss. Our results indicate that weight loss due to negative energy balance depletes intramyocellular lipid storage without affecting intermediate molecules of lipid metabolism, such as intramyocellular diglycerides.