BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) also known as serum platelet activating factor acetylhydrolase (PAF-AH) activity constitutes a novel risk marker for cardiovascular disease. Leukocytes constitute one main cellular source of circulating Lp-PLA2. The aim of the present study was to evaluate the association of both serum and leukocyte PAF-AH activities with fat distribution and lean tissue. One hundred healthy volunteers without cardiovascular disease history participated in this study (n = 52 men, 44 +/- 13 years and n = 48 women, 43 +/- 13 years). Body composition was assessed with dual-energy X-ray absorptiometry, while anthropometrical indices were also measured. The activity of Lp-PLA2 and levels of lipid and glycemic parameters were determined in fasting samples. RESULTS: Mean Lp-PLA2 activity was 24.8 +/- 4.5 and 19.6 +/- 5.0 nmol/min/mL in men and women, respectively (P < 0.001). Mean activity of PAF-AH in leukocyte homogenates was 386 +/- 127 pmol/min/mg and 292 +/- 92 pmol/min/mg in men and women, correspondingly (P < 0.001). In multiple regression models upper and total adiposity measures were positively associated with Lp-PLA2 activity in men after adjusting for LDL-cholesterol, age, smoking, hs-CRP and physical activity, whereas no associations were found with PAF-AH leukocyte homogenates activity. Hierarchical analysis revealed that the variables with the highest explanatory ability of Lp-PLA2 activity in men, were DXA deriving L1-L4 region of interest and arms fat (increase in R2 = 0.136, P = 0.005 and increase in R2 = 0.118, P = 0.009, respectively), followed by trunk fat and total fat. In women, no association of body composition variables with Lp-PLA2 nor PAF-AH leukocyte homogenates activity was found. CONCLUSION: Lp-PLA2 activity is differentiated across levels of adiposity and topology of adipose tissue, whereas no association was found regarding PAF-AH leukocyte homogenates activity. Our findings suggest that Lp-PLA2 may compensate for the adiposity-associated increases in inflammatory and oxidative burden, in men.