The pathogenesis of ketamine cystitis (KC) has been recently linked with immune response to patients but the same has not yet been established. Hence, this study aims to propose a possible immune mechanism of irreversible bladder damage caused by KC. A total of 53 KC patients and 21 healthy volunteers as controls have been retrospectively assessed. The levels of serum immunoglobulin E (IgE), IL-6, and IFN-γ of KC patients were significantly higher than those of controls, whereas the TGF-β levels of KC patients substantially reduced but the IL-2 and IL-4 levels of KC patients were comparable to those of controls. Moreover, the KC patients had significantly higher counts of TH1, TH2, and TH17 cells than those of controls. The immune response of KC users may begin with the IL-6 production and differentiation of TH17 and may be followed by alternating between high expressions of TH1 and TH2. The IL-6 may further suppress the TREG cells which can aggravate chronic inflammation in KC patients and the imbalance in TH17 and TREG cells may involve the pathogenesis of KC. Further investigation is needed to define the role of IL-6 in TH1/TH2/TH17-regulated signaling pathway in ketamine-induced cystitis.