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Purpose. Pleurodesis is used to treat pleural effusions, and a number of agents with varying degrees of efficacy and systemic toxicity have been trialed. This study was conducted to evaluate the efficacy and systemic toxicity of polidocanol in pleurodesis. Methods. Thirty albino Wistar rats were divided into three groups of ten rats each. Group 1 (control) was given isotonic saline, group 2 was given 35?mg/kg tetracycline, and group 3 was given 2.5?mg 0.5% polidocanol, all intrapleurally in a total volume of 0.5?ml. The rats were killed on postoperative day 30 and the macroscopic pleural adhesions and microscopic evidence of inflammation were evaluated. Hepatic, renal, and pancreatic function tests were done and various tissues were microscopically examined to detect systemic toxicity. The mean values of macroscopic and microscopic scoring and biochemical parameters were compared among the three groups. Results. The polidocanol- and tetracycline-treated rats had significantly more adhesions than the control group rats, and polidocanol was more effective for pleurodesis than tetracycline ( P = 0.027). Microscopic scoring was similar in the polidocanol- and tetracycline-treated rats, being significantly higher than that in the control rats. No significant difference was found in the biochemical parameters among the three groups. There were no signs of toxicity in any of the tissues studied microscopically. Conclusions. Polidocanol was found to be a more effective sclerosing agent than tetracycline for pleurodesis. Systemic toxicity was not shown by the biochemical parameters and histopathologic findings.