Aim: Sericin is natural, gumlike protein synthesized from silkworms. Study aims to compare sericin pleurodesis regarding effectiveness, tolerability, side effects, cost effectiveness Method: Adult, male, 12week old Wistar albino rats (n=60); divided to five groups as sericin, talcum powder(TP), doxycycline(dox), silver nitrate(SN) and control. Agents were administrated from left thoracotomy; sacrificed on 12th day. Left hemithorax, heart, liver, and kidneys examined Result: Collagen fibers in visceral pleura investigated; highest ratio of fibers was observed in sericin group, and intensity was higher than in TP group(p˂0.05). Compared to SN, sericin displayed better mesothelial reaction, multi-layer mesothelium was better in sericin(p˂0.05). Foreign body reaction and emphysema were less frequent in sericin compared to TP and dox groups(p˂0.05). The presence of biological tissue was less prominent in sericin compared to all other groups(p˂0.05). Foreign body reaction on thoracic wall was less common in sericin compared with TP and dox(p˂0.05). Presence of biological tissue glue in the thoracic wall was less prominent in sericin compared to TP(p˂0.05) Glomerular degeneration was lower in sericin compared to SN(p˂0.05), and tubular degeneration was less common in sericin than TP(p˂0.05). Pericarditis was less common in sericin compared to dox and SN(p˂0.05) Conclusion: Sericin;low-cost protein with natural glue characteristics. As an intrinsic protein, it protects parenchyma and tissues, and glue like characteristics enables effective pleurodesis. Being cost-effective and better-tolerated agent associated with low potential of side effects, sericin is more effective, less expensive and provides parenchyma protection