There is a current focus on obese adipose tissue as an organ involved in the development of meta‐inflammation—chronic low‐grade inflammation that can predispose the individual to chronic diseases. As an immunomodulating and endocrine organ, it is important to study the relationship between cells found in adipose tissue. Looking into the interplay between two of these adipose tissue cells, adipocytes and adipose tissue macrophages (ATMs), can give scientists information on how to reduce adipose tissue‐derived meta‐inflammation. Hypertrophic adipocytes attract circulating monocytes, which encounter inflammatory molecules when they infiltrate the adipose tissue, causing them to differentiate into macrophages with an inflammatory phenotype. Inflammatory cytokines produced by the ATMs can in turn exacerbate the localized inflammatory condition in the adipose tissue, contributing to the chronic release of inflammatory cytokines from this organ. Certain fatty acids (FAs), like omega‐3 (n‐3) FAs, have long been known to possess anti‐inflammatory properties. The objective of this study was to determine the effects of both n‐3 and n‐6 FAs on inflammatory molecule release by 3T3‐L1 murine adipocytes and RAW264.7 murine macrophages. Macrophages were pre‐incubated with 100 μM of linoleic acid (LA, n‐6), arachidonic acid (ARA, n‐6), or eicosapentaenoic acid (EPA, n‐3) for 24 h, followed by a 6 h, 0.01 μg/ml lipopolysaccharide (LPS) challenge. Fibroblasts were differentiated into adipocytes with the addition of 100 μM of one of the n‐6 or n‐3 FAs throughout the differentiation period, followed by a 6 h, 1 μg/ml LPS challenge once they were fully differentiated. All FA treatments resulted in a significant decrease in macrophage activation (as measured by nitric oxide [NO] production; p<0.001, two‐way ANOVA) and interleukin (IL)‐6 production (p<0.001, two‐way ANOVA) compared to control and LPS‐challenged macrophages. Fatty acid treatment did not affect the release of transforming growth factor (TGF)‐β or monocyte inflammatory protein (MIP)‐1α production by LPS‐challenged macrophages. Adipocytes differentiated with ARA had significantly higher levels of IL‐6 (p<0.05, Tukey’s HSD), compared to control and adipocytes differentiated with LA or EPA. Additionally, ARA resulted in the highest production of MIP‐1α in differentiated adipocytes, followed by EPA (p<0.05, Tukey’s HSD). These results suggest that n‐3 and n‐6 fatty acids have differential effects on inflammatory and chemotactic molecule production in cultured murine macrophages and adipocytes. The n‐6 fatty acid ARA exhibited the strongest immunomodulating effect on both cell types, suppressing activation and IL‐6 production in macrophages, while significantly increasing IL‐6 and MIP‐1α production in differentiated adipocytes. The effects of these fatty acids on co‐incubation of these cell types and total inflammatory molecule production warrants investigation.