Chitin is an attractive option in clinical and biomedical use.It is bio-compatible, -degradable and -absorbable. Due to chitin’s insolubility its de-acetylated derivatives, chitosan or chitosan oligosaccharide (ChOS), are usually used in biomedical settings. In this study the effect of the chitosan derivatives (ChD) ChOS lactate (ChOSL), chitosan <30µm, chitosan and ChOS on human macrophages (MDMs) were studied. Secretion of the macrophage activation markers Chit1 and YKL40, which are an active and an inactive chitinase respectively, was determined. The ChD had no effect on MDM secretion of Chit1 and YKL40, except for ChOSL that decreased YKL40 secretion significantly. It was also of interest whether the ChD had a pro-inflammatory effect. ChOSL proved to be the only ChD that was cytotoxic as measured with XTT assay. This detrimental effect was decreased by inhibiting phagocytosis prior to ChOSL stimulation. ChOSL was also shown to be a potent inflammasome (IS) activator, possibly owing to the decrease in YKL40, which has previously been shown to mediate IS inhibition. The IS activation was not affected by inhibiting phagocytosis or by competitive inhibition. Results show that chitosan and ChOS do not induce activation of macrophages nor an inflammatory response, while ChOSL is a potent activator of the IS and is cytotoxic. Different properties of the ChOS tested are likely due to different levels of acetylation and size, ChOSL being smaller and more similar to chitosan.