This paper presents a new microstrip implantable antenna (MIA) design based on the two-arm rectangular spiral (TARS) element for ISM band (Industrial, Scientific, and Medical 2.4–2.48 GHz) biotelemetric sensing applications. In the antenna design, the radiating element consists of a two-arm rectangular spiral placed on a ground-supported dielectric layer with a permittivity ofϵr= 10.2 and a metallic line surrounding this spiral. Considering the practical implementation, in the proposed TARS-MIA, a superstrate of the same material is used to prevent contact between the tissue and the metallic radiator element. The TARS-MIA has a compact size of 10 × 10 × 2.56 mm3and is excited by a 50Ωcoaxial feed line. The impedance bandwidth of the TARS-MIA is from 2.39 to 2.51 GHz considering a 50Ωsystem, and has a directional radiation pattern with directivity of 3.18 dBi. Numerical analysis of the proposed microstrip antenna design is carried out in an environment with dielectric properties of rat skin (Cole–Cole modelϵf(ω),ρ= 1050 kg/m3) via CST Microwave Studio. The proposed TARS-MIA is fabricated using Rogers 3210 laminate with dielectric permittivity ofϵr= 10.2. The in vitro input reflection coefficient measurements are realized in a rat skin-mimicking liquid reported in the literature. It is observed that the in vitro measurement and simulation results are compatible, except for some inconsistencies due to manufacturing and material tolerances. The novelty of this paper is that the proposed antenna has a unique two-armed square spiral geometry along with a compact size. Moreover, an important contribution of the paper is the consideration of the radiation performance of the proposed antenna design in a realistic homogeneous 3D rat model. Ultimately, the proposed TARS-MIA may be a good alternative for ISM-band biosensing operations with its miniature size and acceptable radiation performance compared to its counterparts.