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Background: chitin and its derivates microparticles (MPs) have immunomodulatory activities. In this study, we examined the effect of size, purity and acetylation degree of chitin MPs on CHID1- encoding SI-CLP, involved in inflammation- gene expression in mixed leukocyte culture. Materials and Methods: Small (<40m) and medium(40-70m) sized chitin MPs were prepared by sonication, and they were used in treatment of leukocyte mixed culture in comparison with chitosan and also shrimp shell small-sized MPs. Neutral red uptake assay and microscopic examination of apoptosis were used to assess cytotoxicity of MPs. Finally, following cell treatment with MPs (100 μg/mL) for 48h, expression levels of CHID1 gene were determined by Real Time PCR. Results: Different concentrations of chitinous MPs hadn't any cytotoxic effects. In gene expression analysis, small-sized chitin MPs (<40 µ) resulted in down regulation of CHID1 gene expression (p=0.004), while other MPs didn't change it significantly. Conclusion: Size, purity and acetylation degree of chitin MPs influence their interference in immune cells interactions and it seems small-sized chitin MPs can potentially modulate immune responses through decreasing CHID1 gene expression. Using small-sized chitin MPs may be effective to treat allergies which their treatment strategies rely on modulating the immune responses. [ABSTRACT FROM AUTHOR]