Objective To analyze the effect of Huanglian Jiedu Decoction on immune cells and inflammatory factors in blood-heat psoriasis mice. Methods Forty SKH-1 female nude mice were randomly divided into normal, model, Xiaoyin Granule and Huanglian Jiedu Decoction groups, with 10 mice in each group. Except the normal group, all the other groups were established blood-heat psoriasis models, and were treated with normal saline, Xiaoyin Granule and Huanglian Jiedu Decoction after successful modeling, respectively. The psoriasis area and severity index(PASI) in each group was evaluated one day after modeling, 1 day before administration and one week after administration. The changes of serum granulocyte colony-stimulating factor(G-CSF), interleukin-10(IL-10) and IL-17 in each group were detected one day before administration and one week after administration, and the expression of CD4, CD8 and CD11c in serum were assayed. Results PASI in model, Xiaoyin Granule and Huanglian Jiedu Decoction groups increased one day before administration and one week after administration, and were higher than those in the normal group. PASI in Xiaoyin Granule and Huanglian Jiedu Decoction groups decreased one week after administration. The levels of IL-17 in model, Xiaoyin Granule and Huanglian Jiedu Decoction groups were lower than those in the normal group one day before and one week after administration, while the levels of G-CSF and IL-10 were higher than those in the normal group. In Xiaoyin Granule and Huanglian Jiedu Decoction groups, IL-17 increased one week after administration, while G-CSF and IL-10 decreased one day before administration. The expression of CD4 in model, Xiaoyin Granule and Huanglian Jiedu Decoction groups was lower than that in the normal group one day before and one week after administration, while CD8 and CD11c were higher than those in normal group. One week after administration, the expression of CD4 in Xiaoyin Granule and Huanglian Jiedu Decoction groups increased, while CD8 and CD11c decreased. Besides, no toxic and side effects were observed in each group. Conclusion Huanglian Jiedu Decoction can effectively regulate immune cells and inflammatory factors in mice with blood-heat psoriasis and promote the regression of skin lesions in mice.