Background: Hydroxyethyl Starch (HES) 130/0.4 (6%) is a commonly used intravascular volume expander with antiinflammatory and antioxidant properties. In this study, we aimed to compare the histopathologic activity of HES 130/0.4 (6%) with various widely-used agents in pleurodesis. Methods: Forty male Wistar-Albino rats were divided into five groups: controls, povidone-iodine recipients (PI group), sterile talcum recipients (Talcum group), autologous blood recipients (AB group) and HES 130/0.4 (6%) recipients (HES group). Thirty days after application of agents, pleural and lung tissues were resected. Evaluation was performed via macroscopic scoring (adhesion) and specimens were stained with H&E for microscopic examination (inflammation and fibrosis). Results: HES recipients had significantly higher adhesion compared to controls (lower grade 0, higher grade 1 frequency vs. controls), they were found to have significantly lower frequency of grade 2 adhesion (vs. PI, Talc and AB) and grade 3 adhesion (vs. AB), indicating that the adhesion-generating properties of HES were only superior to the control group. HES recipients had significantly higher inflammatory grades compared to controls (lower grade 0, higher grade 1 frequency), while they had lower grades compared to the PI, Talc and AB groups. Although the PI, Talc and AB groups were statistically similar in most comparisons, we observed a trend towards higher success with the use of Talc and especially AB. Conclusion: Our results do not support a role for HES in pleurodesis. We believe that the autologous blood method remains as an effective and successful procedure without side effects.