This study evaluated the extracellular matrix (collagen and elastic fibers) in pleurodesis induced by intrapleural talc (TL) or silver nitrate (SN). Study subjects were 420 rabbits divided into two groups and sacrificed from 15 min to 12 months after the injection of the sclerosing agents at intervals previously defined. Pleural adhesions and fibrosis were graded (0-4), and the collagen and elastin were quantified. The maximum score of the pleural adhesions was observed two months after TL (2.80 +/- 0.99) and 15 days after SN (3.75 +/- 0.25). More intense pleural adhesions were observed in the SN group from day 5 (p < 0.05). Pleural thickness and pleural fibrosis were, in general, significantly higher after SN (p < 0.05). Increased deposition of collagen and elastin was observed in both groups but was more evident in the SN group. In the TL group, a linear correlation was observed between pleural adhesions and fibrosis (r = 0.775), between pleural adhesions and collagen (r = 0.779), and between fibrosis and collagen (r = 0.709). In the SN group, these correlations were acceptable (r = 0.605, 0.665, and 0.663). The elastin presented a correlation of 0.707 (p < 0.001) in the TL group and of 0.564 (p < 0.001) in the SN group. In conclusion, intrapleural 0.5% silver nitrate and talc (400 mg/kg) are effective in the induction of pleurodesis. However, the intensity of adhesions and the richness of collagen after SN, in combination with the early onset of tissue remodeling, demonstrate the local superiority of this agent. Considering the easy availability and instillation, the low cost, and the absence of important side effects, silver nitrate might be considered as a sclerosing agent to induce pleurodesis in humans.