Objective: To explore the efficacy of Bifidobacterium combined with mucopolysaccharide polysulfate encapsulation and budesonide cream in the treatment of chronic eczema and its influence on inflammatory factors and peripheral blood T lymphocyte subsets. Methods: A total of 110 patients with chronic eczema admitted to the Fifth People’s Hospital of Hainan Province from June 2020 to December 2021 were randomly divided into a control group and an observation group (n=55 in each group). The control group was treated with mucopolysaccharide polysulfate package + budesonide cream, and the observation group was treated with Bifidobacterium on the basis of the control group. The clinical efficacy, pruritus, lesion area, lesion severity score, and serum inflammatory factors [interferon-γ (IFN-γ), interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α)] and peripheral blood T lymphocyte subsets (CD4⁺, CD8⁺, CD4⁺/CD8⁺) were compared between the 2 groups before and after treatment. Results: The total effective rate of the observation group was significantly higher than that of the control group (89.09% vs 70.91%, P<0.05). The scores of pruritus, lesion area and lesion severity in the observation group after treatment were significantly lower than those in the control group (all P<0.05). Compared with the control group, the serum IFN-γ level in the observation group was higher, and the serum IL-4 and TNF-α levels were lower (all P<0.05). After the treatment, CD4⁺ and CD4⁺/CD8⁺ were higher and CD8+ was lower in the observation group than those in the control group (all P0.05). Conclusion: Bifidobacterium combined with mucopolysaccharide polysulfate encapsulation and budesonide cream in the treatment of chronic eczema has a good curative effect, which can effectively improve the clinical symptoms of patients. Alleviate inflammation and regulate T lymphocyte subsets may be the mechanism of its curative effect.