Background & aims: Low-grade systemic inflammation and pro-inflammatory pattern of cell membrane fatty acid composition characterize patients affected by type 2 diabetes and metabolic syndrome. We hypothesize that inactivity-induced insulin resistance could affect levels of pro-inflammatory fatty acids in cell membranes. Methods: Thirty healthy, male, young volunteers were investigated before and after 35-day experimental bed rest. Diet composition was adapted to previous dietary habits. Fatty acid composition of erythrocyte membranes was analyzed by gas-chromatography using flame ionization detector. Results: Following bed rest, the HOMA index of insulin resistance significantly increased by +51 +/- 11% (P < 0.01). Bed rest was associated with increased n-6 polyunsaturated (+4.7 +/- 2.2%; P < 0.01) and decreased monounsaturated (-4.8 +/- 1.5%; P < 0.01) fatty acid content in erythrocyte membranes. Fractional content of arachidonic acid increased by +14 +/- 12% (P = 0.01) following inactivity. Delta 5 and Delta 9 desaturase indexes, as estimated from product-to-precursor ratios, significantly diminished following bed rest from 9.6 +/- 0.4 to 8.4 +/- 0.3 (P < 0.001) and from 0.72 +/- 0.02 to 0.69 +/- 0.01 (P < 0.05), respectively. The n-3 fatty acids, alpha-linolenic and eicosapentaenoic, were decreased (P = 0.05) following inactivity by 4.7 +/- 13.2% and 3.8 +/- 5.2%, respectively. Conclusions: Inactivity-mediated insulin resistance was associated with altered 6,5 and 6,9 desaturase indexes and with pro-inflammatory fatty acid pattern in erythrocyte membranes. These abnormalities could contribute to the low-grade inflammation associated to inactivity. (c) 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.