Physiological and ultrastructural investigations have been carried out on Procambarus clarkii exposed to sublethal concentrations of Spinosad insecticide. The study showed that the highest mortality percentage was 88% for males and 70% for female occurred at 64 × 10³ ppm Spinosad. The lethal toxicity (LC50) was 24.1 g/l and 29.8 g/l for males and females respectively. Exposure to 1/2 LC50 (12.07 g/l). Spinosad for 7 days caused many physiological disorders including decrease the haemolymph glucose levels and elevated uric acid levels. 12.07 g/l Spinosad resulted in a significant decrease in the total proteins of haemolymph, hepatopancreas and muscles in both males and females. The total cholesterol and triglycerides levels were significantly increased in both haemolymph and hepatopancreas and decreased in muscles of males. On the other hand, cholesterol and triglycerides levels were significantly decreased in haemolymph, hepatopancreas and muscles of females. TEM examinations of male hepatopancreas exposed to 12.07 g/l Spinosad for 7 days revealed ruptured microvilli of absorptive cells, deformed mitochondria, destructed rough endoplasmic reticulum, vacuolated cytoplasm, pyknotic nuclei and appearance of vesicles containing small dark granules.