Objectives: Bacterial endotoxin as biological stress by multiple organs failure causes lysosomal enzyme leakage. Lysosome as a basic cytoplasmic organelle in animal tissues contains hydrolytic enzymes capable of degrading various cellular constituents. In this study protective effect of Cortisone acetate and hydrocortisone 21-sodium hemisuccinate on lysosomal damage and its association with change level of serum and hepatic acid phosphatase activity investigated. Methods: In this study, 30 rats equally divided to Control, tolerance and Endotoxin groups. The tolerance group (12.5 mg/kg body weight intramuscularly injection Cortisone acetate for 3 days and on the 4th day, the intravenous injection 12.5 mg/kg of hydrocortisone 21-sodium hemisuccinate). The induce endotoxin shock in rats with 2.5 mg/kg body weight intravenous injection of Salmonella endotoxin. Partial purification and beta-glucuronidase activity were determined by sephadexG75 chromatography and Polyacrylamide Gel Electrophoresis. Results: The results of this study shown a significant different in level serum and homogenate acid phosphatse activity in Tolerance group compared with the other groups (P<0.05). Also enzyme especial activity in all steps of purification, in Endotoxin group was more than the other groups (P<0.05). Conclusion: Endotoxin shock as biological stressor by induction of lysosomal enzymes into the cell plays an important role in deterioration of cells. Also, it seems that protection of these particles by injection of cortisone acetate and hydrocortisone 21-sodium hemisuccinate can a significant resistance to induced stress by endotoxin shock
