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Clenbuterol, a β-adrenoceptor agonist has been reported to induce skeletal muscle hypertrophy. However, it has also been known to reduce aerobic exercise performance and deleteriously affect endurance and sprint exercise performance in rats. In the present study, chronic administration of clenbuterol (2 mg/kg body weight; 30 days) resulted in various ultrastructural changes in three different type of muscles viz. gastrocnemius a mixed fiber type, anterior latissimus dorsi (ALD) predominantly fast twitch type and diaphragm largely oxidative type of muscle. Most prominent changes included mitochondrial swelling, matricular vesiculation in mitochondria, mitochondrial hyperplasia, sarcoplasmic vesiculation and intermyofibrillar dilations. Increase in cross sectional area of both subsarcolemmal (170, 167, and 79%) and intermyofibrillar (129, 134, and 84%) mitochondria is noticed in gastrocnemius, ALD and diaphragm respectively. The ultramicroscopic and morphometric results suggest drug-induced defects in contractile and oxidative activity.