The chondroitin sulfates (CSs) constitute an important group of biomacromolecules in the extracellular matrix. However, limited information is available about their specific biological functions. This study aimed to define the interactions between cells and various types of CS. The effects of CSs on cellular activities and the cell cycle were evaluated using cell culture, RNA interference, real-time polymerase chain reaction, flow cytometry, wound healing and contraction models. The results showed that C-6-S promoted both cell proliferation and adhesion, while C-4-S promoted proliferation but inhibited adhesion. Moreover, knockdown of chondroitin inhibited cell proliferation and migration, as well as arresting cells in the G(2)/M phase. Also, both C-4-S and C-6-S promoted wound closure in a two-dimensional wound model, whereas only C-6-S inhibited wound contraction in a three-dimensional wound model. This study illustrates that the interaction between cells and different CSs are specific and sulfate-group-dependent. These findings provide useful information for better applications of CSs for wound healing.