A number of mediators are involved in the inflammatory processes that affect joints and vascular wall of patients with rheumatoid arthritis (RA). Tumour necrosis factor alpha (TNFa) is one such mediator, and it is widely regarded as an important target for anti-rheumatic treatment. Most recent studies show that anti-TNFa medication suppresses inflammation and reduces overall activity of RA. The aim of the current study was to investigate changes of mean platelet volume (MPV) in response to the 3-month anti-TNFa therapy in RA. Twenty-one RA patients without established cardiovascular disease were recruited for anti-TNFa therapy and underwent thorough clinical and laboratory evaluation at baseline, 2 weeks, and 12 weeks. Anti-TNFa therapy resulted in a significant (p = 0.01) increase in MPV over the duration of the study (7.7 +/- 0.9, 7.8 +/- 1.1, and 8.4 +/- 1.1 fL at baseline, 2 weeks, and 12 weeks, respectively). The results of the study expand perspectives of the use of MPV in conditions associated with high-grade inflammation, particularly RA, for monitoring anti-inflammatory treatment. More prospective studies with large numbers of patients are warranted to ascertain associations of high and low values of MPV with diverse markers of inflammation and vascular pathology.