Inflammation is a normal response towards tissue injury, but may become deleterious to the organism if uncontrolled. The overproduction of reactive species during the inflammatory process may cause or magnify the damage at inflammatory sites. Flavonoids have been suggested as therapeutic agents to avoid such damage, as these compounds exhibit anti-inflammatory activity, through the modulation of oxidative stress and signalling pathways. Both effects may attenuate neutrophils' activities at inflammatory sites. In this study, we investigated the structure/activity relationship of a series of flavonoids on the oxidative burst of human neutrophils in vitro, as a measure of its anti-inflammatory potential. Neutrophils were stimulated with phorbol-12-myristate-13-acetate, and fluorescence and chemiluminescence techniques were used to evaluate the generation of reactive oxygen species. All the tested flavonoids revealed the ability to modulate the neutrophil's oxidative burst. From the obtained results, the pivotal role of the catechol group in the B-ring was evidenced as well as the minor importance of the hydroxylations in the A-ring, which did not appear to be determinant for the activity, although clearly influencing the lipophilicity of the tested flavonoids. It is also clarified the importance of the methylation in the OH group at the B-ring catechol moiety. In conclusion, the obtained results uncover new possible strategies for the resolution of inflammatory processes, using flavonoids to modulate neutrophil's oxidative burst.