Background: Obesity, an independent cardiovascular disease risk factor, is the leading cause of death in the world. It has been previously shown that arterial stiffness,which is an index of cardiovascular disease, is significantly higher in Japanese overweight and obese men. Increased levels of pentraxin3 (PTX3), a novel anti-inflammatory substance mainly produced in the atherosclerotic region, due to weight reduction has been proposed to reflect an improvement in arterial stiffness. However, this has not been investigated. Methods: Here, we elucidate whether an individual who has significantly increased plasma PTX3 concentration result in a significantly decreased arterial stiffness compared to a smaller change in PTX3 level after a 12-week dietary modified weight reduction program in twenty overweight or obese Japanese men. A well-balanced dietary modification weight-loss program was implemented for overweight and obese men over a course of 12-week. Results: Prior to and after the program, we measured anthropometric variables, blood pressure, arterial stiffness, and circulating biochemistry, including plasma PTX3 concentrations. We then compared the differences in arterial stiffness between two groups, low or high \mathrm{\Delta }PTX3 groups, based on the median of delta of plasma PTX3 levels before and after weight reduction via modified diet habit in men with overweight and obesity. Carotid-femoral pulse wave velocity (PWV) as index of central arterial stiifness and brachial-ankle PWV as index of whole body arterial stiffness were significantly decreased in the high \mathrm{\Delta }PTX3 group after dietary modification. Conclusions: Our present results suggest that PTX3 could be a clinically useful biochemical index for monitoring appropriate arterial function maintenance in obese weight control.