In this work, an attempt has been made to study the subchronic effects of arsenic exposure on the biochemical composition; mainly proteins of the liver tissues of Labeo rohita fingerlings by using Fourier transform infrared (FT-IR) spectroscopic technique. The study was carried out using a Perkin Elmer-Spectrum Rx1 spectrometer. Because of arsenic exposure, significant reductions in the intensity as well as area of amide bands have been observed in the liver tissues. The decreased intensity of the amide bands could be interpreted as the result of alteration of the protein synthesis due to the high affinity of metal compounds towards different amino acid residues of proteins. Further, meso-2, 3-dimercaptosuccinic acid (DMSA) treatment shows the recovery of the protein content in the liver tissues. To confirm that the changes observed are only due to the bio-accumulation of arsenic, the concentration of arsenic in the liver tissues of Labeo rohita was determined by using Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES). It is observed that the arsenic level in the control tissues is found to be below detectable limit, whereas the arsenic exposed liver shows an accumulation of 66.68 ± 0.43 μg/g and DMSA treatment reduces the arsenic content to 17.96 ± 0.19 μg/g. In conclusion, this study gives clear evidence that the use of FT-IR spectroscopy is a powerful approach to achieve more insight into the protein alterations caused by arsenic.