Rubuta ci gaba ga wannan sakin layi - Duke Rannucio I ya mutu a ranar 5 ga Maris 1622. Dan uwansa, Cardinal Odoardo, ya yi aiki a matsayin Regent na Duchy na Parma a madadin dan dan uwansa mai shekaru 10 da sabon Duke Odoardo. Mutuwar Cardinal a watan Fabrairun 1626 ta ba da damar Margherita, yanzu Duchess Dowager, ta zama sabon Regent ga ɗanta. Shekaru 2 na mulkinta ya gudana a lokacin Yakin Shekaru talatin; ta yi nasarar tabbatar da kwanciyar hankali a cikin Duchy, tana kiyaye tsaka tsaki. A Yaƙin Gasar Mantuan
ta goyi bayan Charles Gonzaga, Duke na Nevers, wanda ya zama Duke na gaba na Mantua da Montferrato.