Background: Adiponectin is an anti-inflammatory adipokine that acts through adiponectin receptors 1 and 2 (AdipoR1/AdipoR2). We recently showed that under a T2 environment, adiponectin, via AdipoR1, promotes the IL-10 expression in cultured human circulating Tregs. We here sought to determine the effect of allergic inflammation on IL-10 production in lung AdipoR1⁺ Tregs in vivo. Method: BALB/c mice were sensitized and subsequently challenged with ovalbumin (OVA) on five consecutive days. Control mice were challenged with PBS. Lung Tregs, based on Foxp3 and Helios expression, were assessed for AdipoR1 and IL-10 expression by flow cytometry. Adiponectin levels were quantified in BALF and serum by ELISA. Results: We found a significant increase in the expression of AdipoR1 in CD4 T (P<0.001) and Treg (P<0.01) cells in the lung of OVA-challenged mice compared to PBS controls. While AdipoR1 expression in Helios^neg Tregs was more significant than in Helios^pos Tregs (P<0.05), both subsets of AdipoR1⁺ Tregs were increased in OVA-challenged mice compared to PBS controls (P<0.01). Interestingly, IL-10 production in Helios^neg AdipoR1 Tregs was higher in response to OVA than that of PBS (4.8% and 1.6%, respectively, P<0.05), whereas no differences were found in Helios^pos AdipoR1 Tregs. Adiponectin levels in both BALF (P<0.05) and serum (P<0.01) were significantly reduced in allergic mice compared to controls. Conclusion: Collectively, our findings show that allergic inflammation modulates the adiponectin/AdipoR1 axis in the lung, where IL-10 production by Helios^neg AdipoR1 Tregs might play an important role in their attempt to control the allergic response.