Objective Gastric inhibitory polypeptide (GIP) is an incretin. GIP has a direct effect on the adipose tissue where it induces energy accumulation. Inhibition of GIP receptor (GIPR) signaling prevents the development of obesity and insulin resistance induced by high fat diet (HFD). However, it remains unclear whether direct GIP action in the adipose tissue contributes to adiposity in vivo. In this study, we generated adipose tissue-specific GIPR-deficient mice (GIPRfat-/-) and clarified the direct GIP action in this tissue. Methods GIPRfat-/- mice were generated from floxed GIPR mice (LOX) and aP2-Cre transgenic mice (AP2). GIPRfat-/-, LOX, and AP2 mice were fed HFD for 15 weeks. Afterwards, OGTT, ITT, CT scan, and immunohistochemistry (in liver and adipose tissue) were performed. Also, triglyceride (TG) content in liver was measured. Results Expression levels of GIPR mRNA were particularly lower in visceral and subcutaneous adipose tissues of GIPRfat-/-. Body weight gain under HFD was significantly lower in GIPRfat-/- compared to that of control mice (LOX and AP2). Fat mass and adipocyte size did not differ between GIPRfat-/- and control mice. OGTT data showed that glucose and insulin levels were low in GIPRfat-/-, although there was no significant difference. HOMA-IR and ITT data showed that insulin sensitivity was improved in GIPRfat-/- compared to control mice. Furthermore, fat content in liver was significantly lower in GIPRfat-/- compared to control mice. Conclusion The direct effect of GIP on the adipose tissue plays an important role in HFD-induced insulin resistance in vivo.