BackgroundFood allergy has become a global public health problem. This study aimed to explore the possible anti‐allergic effect of vitamin C (VC).MethodsA rat basophilic leukemia (RBL)‐2H3 cell degranulation model was used to assess the effect of VC on degranulation in vitro and an ovalbumin (OVA)‐induced BALB/c mice allergy model was used to assess the anti‐allergy effect of VC in vivo.ResultsIn vitro, VC significantly attenuated the release of β‐hexosaminidase, tryptase and histamine, and also reduced the cytokines production (IL‐4, IL‐6, TNF‐α) significantly (P < 0.05), with the inhibitory effect demonstrating a positive correlation with VC dose. In vivo, compared with the OVA group, the levels of serum IgE and IgG1 of the VC low‐dose (VCL) group (50 mg·kg−1) and high‐dose (VCH) group (200 mg·kg−1) were significantly reduced (P < 0.05). Furthermore, the plasma histamine level was also significantly decreased (P < 0.05). Moreover, the TH2 cell polarization in mice of the VCL and VCH groups were significantly inhibited (P < 0.05), promoting the TH1/TH2 cell polarization balance. Additionally, VC treatment enhanced the expression of CD80 (P < 0.05) in spleens and small intestine tissues, while significantly inhibiting the expression of CD86 (P < 0.05); notably, high‐dose VC treatment was more effective.ConclusionsVC exerted an anti‐allergic effect through inhibiting degranulation and regulating TH1/TH2 cell polarization balance.This article is protected by copyright. All rights reserved.