A possible mechanism by which chronic clenbuterol treatment causes multiple physiological changes in skeletal muscle that leads to reduced insulin resistance in the obese Zucker rat (falfa) was investigated. Animals were gavaged with clenbuterol (CB) (0.8 mg x kg(-1) day(-1)), terbutaline (TB) (1.0 mg x kg(-1)day(-1)), or control (CT) vehicle for six weeks. Oral glucose tolerance and insulin responses were markedly improved in CB rats and impaired in TB rats. CB treatment caused a 24-34% gain in muscle mass in all muscle fiber types, and increases in 3-O-methyglucose transport (2-fold) and GLUT4 concentration (57%) in fast twitch glycolytic (FG) muscle. Oxidative capacity was reduced in both FG (47%) and fast twitch oxidative (FO) muscle (30%), but not in slow twitch oxidative (SO) muscle. Null model analysis for receptor occlusion demonstrated that most functional beta-adrenoceptors were lost in FO (82%) and FG (89%) fibers, but not in SO fibers. We propose that hypertrophy is the result of continuous direct activation of beta-adrenoceptors while loss in oxidative capacity may be the result of receptor down regulation. Improvements in insulin resistance may have been due, in part, to both increases in lean body mass and specific adaptations in FG muscle.