purpose: chemical pleurodesis is a therapeutic tool for the treatment of recurrent pleural effusions, mainly those of neoplastic etiology. in the past, tetracycline was the sclerosant agent of choice in clinical practice, but presently, there is no consensus about an ideal agent. the aim of this study was to evaluate the effectiveness of macrolides (azithromycin and clarithromycin) or quinolones (levofloxacin and gatifloxacin) in inducing experimental pleurodesis in rabbits. method: forty new zealand rabbits randomized into groups of 10 received (at a total volume of 2 ml for each animal) 1 of the 4 drugs by intrapleural injection. after 28 days, the animals were euthanized and the pleural cavity was evaluated macroscopically and microscopically. results: the intensity of the macroscopic adhesions was mild in all groups. on microscopic analysis, minimal pleural fibrosis and inflammation were observed in all animals. conclusion: the macrolides (azithromycin or clarithromycin) and the quinolones (levofloxacin or gatifloxacin) when injected into the normal pleural space of rabbits are not effective in promoting pleurodesis. additional research is required to identify sclerosing agents capable of inducing pleurodesis.