SUMMARY Dysregulation of immune cells and/or altered inflammatory signaling have been implicated with reproductive dysfunction. Physiological changes leading to perturbations in the profile of immune cells and/or pro‐inflammatory cytokines in or around female reproductive tissue could potentially have profound effects on ovarian function. Obesity is associated with chronic low‐grade inflammation due, in part, to increased immune cell infiltration and inflammation in visceral adipose depots. This study investigated the impact of diet‐induced obesity on immune cell infiltration and inflammation in peri‐ovarian adipose tissue and mRNA expression of key inflammatory markers and microRNAs (miRs) in ovarian tissue. Six‐week‐old female C57Bl/6J mice were fed a standard chow or high‐fat diet (HFD; 60% kcal fat) for approximately 7 months, at which time peri‐ovarian adipose tissue and ovarian tissues were collected. Histological analysis of peri‐ovarian adipose tissue from obese mice revealed increased (P < 0.05) adipocyte size and the presence of crown‐like structures, the morphological presentation of infiltrating immune cells in adipose tissue, along with increases (P < 0.05) in the mRNA levels of markers of T‐cells, activated macrophages, inflammatory cytokines, and chemokines. Ovarian mRNA levels of Il1b, Il6, Tnfa, p55, p75, Ccl2, Ikbkb, and Rela were higher in obese tissue (P < 0.05), with a strong trend (P = 0.06) for an increase in Nos2 and RELA protein. Additionally, ovarian miR125b and miR143 levels were decreased (P = 0.1). These data demonstrate that diet‐induced obesity elevates expression of inflammatory‐mediator genes in both the ovary and surrounding adipose depot, potentially negatively affecting ovarian function. Mol. Reprod. Dev. 80: 948–958, 2013. © 2013 Wiley Periodicals, Inc.