ABSTRACT Background and objective:  The mechanism by which iodopovidone achieves pleurodesis is unknown. This study investigated whether iodopovidone is as effective as doxycycline in producing pleurodesis and whether systemic corticosteroids diminish its efficacy. Methods:  Four groups of seven New Zealand rabbits were assigned to the following intrapleural treatment groups: 2 mL of 2% iodopovidone, 2 mL of 4% iodopovidone, 2 mL of 4% iodopovidone plus 0.8 mg/kg triamcinolone intramuscularly weekly and 10 mL/kg doxycycline in 2 mL. Pleural fluid was collected 24, 48 and 72 h after intrapleural injections and analysed for WCC, protein and LDH levels. The rabbits were killed 2 weeks after the injections. Pleurodesis was graded macroscopically on a scale from 1 to 8. The degree of microscopic pleural fibrosis and pleural inflammation was graded from the HE stain slides. Results:  The mean volume of pleural fluid as well as the mean total WCC was significantly lower in the steroid‐treated group than in the other groups. The degree of the resulting pleurodesis was similar in the 2% iodopovidone (7.00 ± 1.29), 4% iodopovidone (7.71 ± 0.76) and doxycycline (7.14 ± 0.90) groups (P > 0.05) whereas the pleurodesis score of the steroid group (3.71 ± 1.98) was significantly lower than all other groups (P < 0.05). The degree of microscopic pleural fibrosis and pleural inflammation was significantly lower in the steroid group than in the 2% iodopovidone or 4% iodopovidone group. Conclusions:  Both 2% and 4% iodopovidone can induce pleurodesis as efficaciously as doxycycline in rabbits. Systemic corticosteroids significantly decrease the efficacy of iodopovidone in producing pleurodesis. This study used a rabbit model to compare the effectiveness of iodopovidone in causing pleurodesis with that of doxycycline and investigated the mechanism by which iodopovine acts. Iodopovidone produced effective pleurodesis via an inflammatory mechanism and corticosteroids significantly decreased its efficacy.