Addition of roxarsone can significantly improve the growth of broiler chickens (Gallus gallus domesticus). Nevertheless, this application will lead to the contamination of the environment as well as animal products. Understanding the response of genes to roxarsone may bring about the discovery of new, safer substitutes. In this study, we monitored the expression of 8,935 genes in chicken breast muscle using microarrays. Analysis showed that 30 genes, such as the interleukin 3 regulated nuclear factor (NFIL3), the regulatory factor X-associated ankyrin-containing protein (RFXANK), the cleavage and polyadenylation-specific factor 3 (CPSF3), and the FK506 binding protein 9 (FKBP9), have consistently up or downregulated (fold change ≥1.5 or ≤0.6, P < 0.05, false discovery rate ≤0.05) throughout the medication periods. The results from microarray analysis were validated by real-time quantitative PCR. Further functional investigation showed that 13 of the identified genes are well documented, and surprisingly, 11 (85%) of these are related to immunity (5 are immunity and defense related, 4 are immunodeficiency disease related, 2 are immunosuppressive drug related), and the remaining 2 are energy metabolism related. These findings may suggest that supplement of roxarsone can improve the immunity of chickens through regulating the expression of associated genes, and as a result contribute to the growth promotion. Further research on the encoded proteins of the differentially expressed genes should provide more evidence for the potential mechanism.