Background and Purpose: Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme within the NAD+ salvage biosynthetic pathway and also a cytokine modulator with effects on inflammation and fibrogenesis. FK866 (NAMPT inhibitor) has shown anti-inflammatory properties. However, FK866-induced depletion of NAD+ may also impair liver bioenergetic metabolism during Chronic Liver Disease (CLD). The aim of this study was to evaluate the effects of NAMPT inhibition and NAD+ restoration on experimental CLD. Experimental Approach. CCl4-induced liver cirrhosis was established after 6 weeks. Treatment groups (n=5 mice per group) included: 1) vehicle; 2) CCl4 control; 3) Silymarin + CCl4; 4) FK866 + CCl4; and 5) NMN+FK866+CCl4. At the end of the experimental induction and treatments, mice were sacrificed and liver was collected for weight, and paraformaldehyde fixed for histological characteristics of inflammation and fibrosis, as well as NAD+/NADH determination by colorimetric assay. Liver function tests were performed from blood sample. Statistical analysis was performed by T-test. Key Results. NAMPT inhibition resulted in a mild attenuation of histological and biochemical features of the CCl4-induced liver damage. NAD+ restoration, by the concomitant administration of its precursor NMN, resulted in a significant improvement of the histological characteristics; evidenced by a lower inflammatory infiltrate and fibrosis as well as lower levels of bilirubin. NAMPT inhibition and adequate NAD+ restoration were confirmed by a colorimetric assay of NADH and NAD+ and biochemical features were measured by routinary Liver Function Tests. Conclusion and implications. This study shows that NAMPT inhibition concomitant to NAD restoration significantly attenuate experimental liver damage.