Abstract: Maculosin is a kind of cyclic dipeptides resulting from double condensations between L-proline and L-tyrosine. It was purified from the fermentation broth of strain CGD12, an Aspergillus fungi isolated from Rhizophora stylosa rhizosphere soil in the previous study. In the present study, lactate dehydrogenase(LDH)assay was applied to detect the cytotoxicity of Maculosin in lung fibroblasts. Real-time quantitative RT-PCR was used to assess its effects on the fibrotic-related gene expression. The results showed that Maculosin inhibits the activation of lung fibroblasts and attenuates the accumulation of extracellular matrix(ECM)induced by exogenous TGF-β₂. Further study suggested that the anti-fibrotic activity of Maculosin may be related to repressing the expression of inflammatory cytokines and promoting the process of ECM degradation.