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Background Yaks living in the high-altitude hypoxic environment of Tibetan plateau (3600 m) have special gut microbes. However, it is still little research on yak probiotics until now. Therefore, the purpose of our study was to evaluate the growth promoting effect, antioxidant capability, immune effect, and anti-inflammatory ability of Bacillus subtilis and Bacillus velezensis isolated from Tibetan yaks in mice model. Results The results showed that the isolated strains supplementation not only improve the growth performance but also increased the length of villus in the small intestine and intestinal digestive enzyme activity. Importantly, we observed that the T-AOC, SOD, and GSH-PX levels were increased and the MDA content was reduced in probiotic-treated mice, which implied that probiotics supplementation can ameliorate the antioxidative activity of mice. The levels of AST and ALT correlated with the hepatic injury were reduced and the levels of AKP, TP, GLB, ALB, Ca, and P were markedly higher than those in the control group. Additionally, mice treated with probiotics exhibited higher serum IgG, IgM and IgA, which can reflect the immune status to some extent. At the same time, the major pro-inflammatory factor TNF-α, IL-6, and IL-8 were down-regulated and the anti-inflammatory factor IL-10 was up-regulated compared with the control groups. Conclusions In conclusion, these results demonstrated that Bacillus subtilis and Bacillus velezensis supplementation can increase overall growth performance and ameliorate the blood parameters related to inflammation and immunity of mice. Electronic supplementary material The online version of this article (10.1186/s12934-019-1161-6) contains supplementary material, which is available to authorized users.