Decompression sickness (DCS) is a systemic syndrome that can occur after an environmental pressure reduction. Previously, we showed that the plasmatic tetrameric form of transthyretin (TTR) nearly disappeared in rats suffering DCS but not in asymptomatic ones. In this pilot study, we assessed whether the resistance to DCS could be associated with polymorphism of the gene of TTR. For this study, Sanger sequencing was performed on purified PCR products from the liver of 14‐week‐old male and female standard and DCS‐resistant rats ( n = 5 per group). Hepatic TTR mRNA expression was assessed by RT‐qPCR in 18–19 week‐old male and female standard and resistant rats ( n = 6 per group). There is a synonymous single nucleotide polymorphism (SNP) on the third base of codon 46 (c.138 C > T). The thymine allele was present in 90% and 100% of males and females standard, respectively. However, this allele is present in only 30% of DCS‐resistant males and females ( p = 0.0002301). In the liver, there is a significant effect of the resistance to DCS ( p = 0.043) and sex ( p = 0.047) on TTR expression. Levels of TTR mRNA were lower in DCS‐resistant animals. To conclude, DCS resistance might be associated with a SNP and a lower expression of TTR.