Aim To establish early experimental atherosclerosis (As) rat model, and to investigate peripheral CD4⁺CD25⁺ regulatory T cells (Treg)/T helper 17 cells (Th17) imbalance and the effects of all-trans-retinoic acid (ATRA) on the balance in the model.Methods Fifty 8-week-old Sprague Dawley rats were randomly divided into 5 groups: the normal group, cholesterol diet group, immune injury group, cholesterol diet plus immune injury group, and cholesterol diet + immune injury + ATRA group (ATRA group). Rats in normal group and immune injury group were fed with normal diet, and other groups were fed with cholesterol diet. Rats in immune injury group, cholesterol diet plus immune injury group and ATRA group were immunized by ovalbumin. Rats in ATRA group were treated with ATRA. For all the 5 groups, the samples of blood and aorta were obtained after 16 weeks. The levels of serum lipids and cytokines were measured by ELISA Histological changes in aorta were analyzed by HE staining, and the frequencies of Th17 and Treg cells were detected by flow cytometry.Results A rat model of early As was established successfully. The results of HE staining showed that there was an edematous thickening in the intima and a mild atrophy in the membrane of cholesterol diet plus immune injury group, and there was also a less extent on pathological changes in immune injury group and ATRA group. Serum total cholesterol (TC) and low density lipoprotein cholesterol (LDLC) concentrations in cholesterol diet group and cholesterol diet plus immune injury group were markedly increased compared with those in normal group and immune injury group (all P<0.05), but the levels of serum lipids in ATRA group had no significant difference compared with those in other groups. Expression of Treg and relative cytokines (interleukin-10 (IL-10), transforming growth factor beta (TGF-β)) was significantly lower while expression of Th17 and relative cytokines(IL-17, IL-6) was obviously higher in immune injury group and cholesterol diet plus immune injury group than those in normal group and cholesterol diet group (all P<0.05). The levels of Treg and relative cytokines were significantly increased while the levels of Th17 and relative cytokines in ATRA group were markedly decreased than those in cholesterol diet plus immune injury group (all P<0.05).Conclusions An early As rat model was successfully established by immune injury and cholesterol diet. The shift of the Th17/Treg balance from Treg cells towards Th17 cells exists in rat model, and ATRA may play an important role in inhibiting As development by influencing the peripheral Th17/Treg balance.