Objective To study the degrees of adrenocortical inhibition after the action of glucocorticoid drugs,and the differences in its drug-induced syndromes in five mouse strains. Methods ICR, BALB/ c, C57BL/6J, KM andnude mice were selected. Prednisolone was used as the drug for intervention. There were 16 mice of each strain, eight-eachin the normal control group and prednisolone group. Prednisolone (0. 5 mg/ kg·d) was administered for 14 consecutive daysin the prednisolone group. The body weight of mice was recorded every day, and TCM diagnostic information were detectedby the experimental methodology of syndrome differentiation and treatment in mice on the 14th day. Mice was sacrificed andtheir spleen and thymus were weighed, and the organ indexes were calculated. Serum levels of corticosterone andadrenocorticotropic hormone (ACTH) were measured by ELISA. Gene expression of Star(steroidogenic acute regulatoryprotein), Cyp11a1(cytochromes P450 11A1), Cyp21a1(cytochromes P450 21A1), Cyp11b1(cytochromes P450 11B1)and Cyp11b2(cytochromes P450 11B2) in the adrenal glands were detected by real-time fluorescent quantitative PCR.Protein expression of LDLR(low-density lipoprotein receptor), SRBI(scavenger receptor class B member 1) and StAR(steroidogenic acute regulatory protein)was detected by Western blot. Results Compared with the control group of therespective strains, the body weight of ICR mice decreased significantly 7 days after prednisolone administration ( P <0. 01), BALB/ c mice decreased significantly 13 days after prednisolone administration ( P < 0. 01), C57BL/6J micedecreased significantly 5 days after prednisolone administration ( P < 0. 01), and nude mice decreased significantly 13 daysafter prednisolone administration ( P < 0. 05). Prednisolone administration resulted in a significant decrease in the gripstrength and a significant decrease in the mean temperature of the body trunk of ICR mice ( P < 0. 05). Prednisoloneresulted in a significant decrease in the spleen weight of ICR mice and nude mice ( P < 0. 01) and a decrease in the splenicindex of nude mice ( P < 0. 05), whereas prednisolone administration resulted in a significant decrease in the thymic weightand thymic index of ICR, C57BL/6J and KM mice ( P < 0. 01). Prednisolone administration significantly decreased theserum corticosterone level in BALB/ c and KM mice ( P < 0. 05), and serum level of ACTH in BALB/ c mice ( P < 0. 01).Prednisolone significantly downregulated the Cyp21a1 expression in ICR mice ( P < 0. 05),Star expression in C57BL/6Jmice ( P < 0. 01), Cyp11a1 and Cyp21a1 expression in KM mice ( P < 0. 01), and Star and Cyp21a1 expression in nudemice ( P < 0. 05). In addition, prednisolone inhibited expression of LDLR and StAR in the ICR and KM mice. ConclusionsThe prednisolone-induced deficiency syndrome in mice is mainly characterized by “qi deficiency”, which is involved in the“kidney state” and “ spleen state”. The basis of this deficiency syndrome is primarily inhibition of expression ofadrenocortical steroid synthase and function of the pituitary-adrenocortical axis. ICR mice is suggested to be used for studies of glucocorticoid-induced asthenia.