BACKGROUND: In acute respiratory distress syndrome (ARDS) obesity is associated with lower mortality but the mechanism(s) have not been elucidated. METHODS: We aimed at assessing plasma biomarker levels interleukin-8 (IL-8), matrix metalloproteinase-7 (MMP-7), Toll-like receptor 2 (TLR-2), tumor necrosis factor-α (TNF-α) and procalcitonin (PCT) at baseline and 3 days later in 20 consecutive moderate-severe ARDS consecutively admitted to our Center. RESULTS: Our population includes 20 consecutive mechanically ventilated patients with moderate-to severe ARDS. The incidence of obesity was 40% (8/20). No differences were detectable between obese and normal patients in baseline characteristics. In particular, ICU mortality was comparable between the two subgroups. No differences were detectable between the two subgroups at baseline and after 72 hours in biomarker plasma levels. When examining the behavior of each biomarker, obese patients showed a significant increase in MMP7 and TLR-2 values at 72 hours in respect to baseline, differently from normal patients. CONCLUSIONS: Our data strongly suggest that obese patients with moderate to severe ARDS have an altered inflammatory response to acute lung injury, since a significant increase in MMP-7 and TLR-2 was detectable at 72 hours only in these patients. Further investigations are needed to confirm our results in larger cohorts.