Objective To compare the effects of the complex triamcinolone acetonide-hydroxypropyl-β-cyclodextrin (TA-CD) on in vitro inflamed primary human articular chondrocytes in the presence or absence of the mixture hyaluronic acid-Chitlac, a lactose-modified chitosan (HA-CTL). Design Changes in cell viability and pro-inflammatory cytokines gene expression were analyzed in human chondrocytes using an in vitro model of macrophage-mediated inflammation. Human monocytes U937 were differentiated to macrophages by phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharides (LPS). The anti-inflammatory effects of the complex TA-CD and HA-CTL mixture were assessed on chondrocytes exposed for 24 hours to U937 conditioned medium (CM), by quantitative polymerase chain reaction analysis. Results The TA-CD viability was enhanced by the presence of the HA-CTL mixture in chondrocyte cultures. The exposure of cells to CM significantly increased interleukin-1β and interleukin-6 gene expression, and when the complex TA-CD was added to the inflamed cells, gene transcription of cytokines was restored to near baseline values, both in the presence or in the absence of HA-CTL mixture. Conclusion The addition of HA-CTL mixture significantly attenuated cytotoxicity induced by TA and preserved the anti-inflammatory effects, thus confirming the chondroprotective role of the HA-CTL mixture.