<b>Background and Objective:</b> Astaxanthin (3,3'-dihydroxy-β-β-carotene-4,4'-dione) is a carotenoid, commonly found in marine environments has been reported to possess versatile biological properties including anti-inflammatory and antioxidant. In this study, the pancreatic protective effect of astaxanthin was investigated in D-Galactosamine-induced pancreas injury in rats. <b>Materials and Methods:</b> In this experimental study, MTT assay was used to determine cytotoxic effects of the Astaxanthin on pnc1 cells. A total of 30 adult albino rats divided into 5 groups, six rats in each. Group I was given an equal amount of distilled water, group II was received 400 mg kg<sup>1</sup> b.wt. D-galactosamine on 15th day, groups III-V were treated with astaxanthin (50 and 100 mg kg<sup>1</sup>) and/or silymarin (50 mg kg<sup>1</sup>) for 14 days + 400 mg kg<sup>1</sup> b.wt. D-galactosamine on the 15th day, respectively. <b>Results:</b> IC<sub>50 </sub>of Astaxanthin against the pnc1 cell line was 92.9 μg mL<sup>1</sup>. The daily oral administration of astaxanthin (50 and 100 mg kg<sup>1</sup>) as well as silymarin (50 mg kg<sup>1</sup>) for 14 days to rats treated with D-galactosamine resulted in a significant improvement in plasma AST, ALT, ALP as well as pancreatic TNF-α, IL-1β, IL-10, NO and VEGF-C gene expression. On the other hand, inducible oral administration of astaxanthin increased the activity of pancreatic GSH, SOD, GPx, GR, CAT and the level of TBARs in D-galactosamine-treated pancreatic of rats. Furthermore, Astaxanthin almost normalized these effects in pancreatic tissue histoarchitecture and MRI examination. <b>Conclusion:</b> The obtained results showed that Astaxanthin protected experimental animals against D-galactosamine-induced pancreatic injury through activation of antioxidant enzymes and IL-10 and inhibition of VEGF-C activation.