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Lactobacillus casei is one of probiotic bacteria which have an antibiotic (tetracycline) resistance encoded by tetM gene. This gene can be unstable which lead to changes in the DNA sequence (mutation) during the adaptation process under sub-lethal dose of tetracycline antibiotic. The aim of the study is to observe the resistance level and genetic instability of tetM gene under sub-lethal dose of tetracycline antibiotic and to examine the effect of gene instability on the antibiotic resistance level of L. casei. This study was conducted by 2 steps e.g. determination of sub lethal dose of L. casei and to isolate L. casei with the highest resistance to tetracycline using adaptation process. This study confirmed that L. casei could survive with sub-lethal dose of 10-50 µg.mL-1 tetracycline and has a lethal dose at 60 µg.mL-1. The concentration of more than 60 µg.mL-1 tetracyline made the instability of tetM gene lead to the survival of L. casei at 70 µg.mL-1 tetracycline after adaptation process.