Recently, vaspin and visfatin/Nampt have been identified as interesting novel adipokines having insulin-sensitizing and insulin-mimetic effects, respectively. However, the relationship between them has not been elucidated; and their circulating levels in type 2 diabetes mellitus (T2DM) have not been adequately studied. Therefore, this study was designed to investigate whether their levels are altered in Egyptian T2DM patients and to study the correlation of these novel adipokines with each other and with insulin resistance, interleukin-6 (IL-6), and other biochemical parameters. The levels of vaspin, visfatin/Nampt, IL-6, insulin, and other parameters were measured in nonobese and obese T2DM patients together with matched healthy nondiabetic control subjects. Vaspin, visfatin/Nampt, and IL-6 levels were measured by enzyme-linked immunosorbent assay, whereas insulin levels were measured by chemiluminescence technique. Vaspin and visfatin/Nampt levels were found to be significantly elevated in nonobese (1.62 ± 0.22 and 25.9 ± 3.44 ng/mL, respectively) and obese T2DM patients (2.76 ± 0.38 and 45.4 ± 4.60 ng/mL, respectively) compared with control subjects (0.42 ± 0.05 and 9.37 ± 1.98 ng/mL, respectively) at P < .01. In addition, vaspin and visfatin/Nampt levels were found to be significantly positively correlated with each other and with other biochemical parameters. In conclusion, both vaspin and visfatin/Nampt might play an important role in the pathogenesis of T2DM. In addition, the 3 adipokines--vaspin, visfatin/Nampt, and IL-6--are significantly interrelated with each other. Other possible mechanisms of action for vaspin should be considered besides the inhibition of unknown substrate proteases.