Using thiophene (which has a moderate resonance energy) as a spacer rather than benzene permits better π-electron delocalization and leads to a large nonlinear optical response. Thus, the nonlinear optical coefficients of a series of macrocyclic thiophene derivatives (C[3T_DA] n with C n symmetry) were studied, and their electronic structures, UV-Vis spectra and static second-order nonlinear optical susceptibilities (β 0) were computed. The calculated results showed that ΔE H-L increased and the UV-Vis spectrum redshifted as the number of C[3T_DA] units increased (one C[3T_DA] unit consists of trithiophene and diacetylene). The value of β 0 calculated by either the ZINDO-SOS or the FF method showed the same trend: the absolute value of β 0 increased as the number of units increased. The value of β 0 predicted by ZINDO-SOS was an order of magnitude larger than that predicted by the FF method. However, the results suggest that macrocyclic thiophene compounds potentially exhibit large static second-order nonlinear optical susceptibilities.